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Hyperglycemia Is Associated with Psoriatic Inflammation in Both Humans and Mice

Published on Jun 1, 2019in Journal of Investigative Dermatology6.29
· DOI :10.1016/j.jid.2019.01.029
K. Ikumi1
Estimated H-index: 1
(Nagoya City University),
Mizuyu Odanaka2
Estimated H-index: 2
(Nagoya City University)
+ 8 AuthorsSayuri Yamazaki27
Estimated H-index: 27
(Nagoya City University)
Abstract
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia. Although it should be determined if psoriasis-like cutaneous inflammation alone can induce hyperglycemia, imiquimod-treated mice showed impairment of insulin secretion without significant islet inflammation. Administration of anti-IL-17A monoclonal antibody improved hyperglycemia in patients with psoriasis and imiquimod-treated mice with psoriasiform features. These results suggest that hyperglycemia is highly associated with psoriasis, mainly through IL-17.
  • References (42)
  • Citations (2)
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References42
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Summary Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin resistance (IR) in obesity, but the physiological role of this mechanism is unclear. It is also unknown whether and how viral infection induces loss of glycemic control in subjects at risk for developing diabetes mellitus type 2 (DM2). We have found in mice and humans that viral infection caused short-term systemic IR. Virally-induced interferon-γ (IFN-γ) directly targeted skeletal muscle to downregulate th...
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#2Daniel B. Shin (UPenn: University of Pennsylvania)H-Index: 3
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Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psor...
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BackgroundTwo phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. MethodsWe randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 pat...
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#1Louis C.S. Gardner (Newcastle University)
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Psoriasis is associated with the metabolic syndrome, an interconnected group of conditions characterized by significant morbidity and mortality, although the causal mechanisms are still under investigation. Ikumi et al. provide evidence of a link—involving IL-17—between psoriasis and hyperglycemia in humans and mice.
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